A "thrifty gene" has been proposed as a genetic defect that would predispose the Pima Indians to store energy very efficiently and account for their high prevalence of obesity. To determine if such genetic differences exist, the thermogenic response to three stimuli - food, norepindephrine, and exercise - were measured during a period of weight maintenance and after three weeks of overfeeding. These studies were done in lean and obese Indians. The major finding to date has been that obese Pimas, though having similar basal plasma concentrations of norepinephrine to causasians, achieve much higher blood concentrations of the hormone during identical norepinephrine infusions. The data suggests that obese Pima Indians have a clearance defect of norepinephrine. Turnover studies will be done to confirm these data.